The preparation of monoclonal antibodies using synthetic polypeptides derived from the variable regions of p21 ras proteins encoded by the family of oncogenes designated ras.sup.H, ras.sup.K, and ras.sup.N was described in U.S. Pat. application Ser. No. 739,416, filed May 30, 1985, entitled RAS ONCOGENE PEPTIDES AND ANTIBODIES, inventors Chizzonite et al. These polyclonal antibodies are each selective for the specific family from whose sequence the immunogenic peptide was synthesized. Thus the antibodies can be used to assay for the presence of the specific ras gene products in a biological fluid specimen.
It is also known in the art to provide ras oncogene antibodies which are selective for the substitution of an amino acid at position 12 of the ras p21 protein. Thus, for example, an anti-p21-ser rabbit polyclonal antibody which binds to v-Ki-ras (serine at position 12) but not to v-Ha-ras (arginine at position 12) protein is an article of commerce (Cetus Diagnostics, Emeryville Calif). Also available are polyclonal antibodies specific for polypeptides with the following changes at position 12: Val, Asp and Arg. These antibodies are provided in kit format useful for analysis of cellular and tissue extracts for the presence of the corresponding mutant proteins. The mutant proteins are thought to facilitate the transformation process in human tumors. Additionally, a monoclonal antibody which is directed against the conserved regions of p21 ras protein thus serving as a pan antibody reactive with all known forms of the p21 protein is also an article of commerce. The pan reactive antibody is indicated to be useful for exploring ras oncogene expression. The preparation of such materials is described by Clark et al., Proc. Natl. Acad. Sci. USA 82, 5280-5284 (1985).
Another changed position in p21ras oncogenes is known to provide proteins that facilitate the transformation process in human tissues. This involves mutation at codon 61 in the p21 ras sequence to provide leucine instead of the glutamine contained in the normal sequence. A monoclonal antibody which could selectively recognize such a change would be extremely useful in identifying the p21Leu61 transforming protein in cells, tissues and biological fluids.